Regulatory Role of Nitric Oxide in Cutaneous Inflammation

Abstract

Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.

Keywords: dermatitis; inflammation.; nitric oxide.

Fig. 1

Schematic diagram of enzymatic production of nitric oxide from L-arginine: Nitric oxide synthases first catalyze 5-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg) to generate N^ω-hydroxy-L-arginine (NOHLA), via activating oxygen at heme and transferring electrons from 1 molecule of nicotinamide-adenine-dinucleotide phosphate (NADPH) to flavin-adenine-dinucleotide and flavin-mononucleotide, followed by oxidation of N^ω-hydroxy-L-arginine, consuming 0.5 molecules of NADPH and one molecule of oxygen, to produce citrulline and nitric oxide. This diagram is modified from previous publications [29, 30].